A marked disturbance in aromatic amino acid metabolism occurs in acute and chronic Trypanosoma brucei gambiense infections of laboratory rodents. The disturbance is characterized by very large increases in urinary excretion of phenylpyruvic acid, 4-hydroxyphenylpyruvic acid, indole-3-pyruvic acid, indole-3-lactic acid, and indole-3-acetic acid concurrent with large decreases in serum concentrations of tryptophan and tyrosine. Such a disturbance can potentially contribute greatly to host pathogenesis in trypanosomiasis, either directly by toxic action of some of the catabolites, or indirectly by reducing host levels of metabolically and physiologically important tryptophan and tyrosine. The increased catabolite concentrations observed may also prove to be useful diagnostically. We propose to determine if tryptophan and tyrosine reduction and/or aromatic amino acid catabolite production occur sufficiently early and extensive in infection to be a primary contributing factor to host pathogenesis. We will do this by concurrently measuring the concentrations of the aromatic amino acids, the aromatic pyruvic acids and their immediate catabolites in body fluids of Microtus montanus throughout the entire course of chronic T.b. gambiense infections. The measurements will be made using high performance liquid chromatography and gas chromatography. We furthermore propose to investigate if important host aromatic amino acid metabolic pathways are affected and if the characteristic changes in activity patterns of infected Microtus are correlated with the changes in amino acid or catabolite levels. Finally, if plasma and urinary catobolite concentrations are sufficiently elevated throughout chronic infections, we will test several published simple chemical assays for possible use as diagnostic tests.